Hyperargininemia is considered to be the least common urea cycle disorder (UCD) encountered in clinical practice, with estimated incidence rates of 1 in 350,000-1,000,000 [1]. The pathogenesis stems from mutations in genes coding for the catalytic enzyme arginase that is necessary for the conversion of L-arginine to urea and ornithine [2] [3]. Hyperargininemia, like the majority of UCDs, is transferred through an autosomal recessive pattern of inheritance, but the clinical presentation differs from other UCDs in terms of the onset of symptoms and their severity [2] [4]. Namely, patients mainly start to develop first signs after infancy, in the period between ages 2 and 4, while severe hyperammonemia that is typical in other UCDs is often absent [2] [4]. Instead, a slowly progressive appearance of neurological manifestations is seen, starting with irritability, failure to thrive, feeding difficulties, and inability to reach appropriate developmental milestones [4] [5]. In the absence of proper therapy, more severe symptoms and signs are noted in a slowly progressive fashion - seizures (generalized tonic-clonic), progressive spastic diplegia, psychomotor and cognitive decline, as well as growth failure [1] [2] [4] [5]. In a subset of cases, episodes of vomiting and lethargy are observed [4]. Furthermore, liver diseases (cholestasis, liver failure, fibrosis, or even hepatocellular carcinoma) can be recognized in some cases of hyperargininemia [3] [6] [7].

• Disability

  Patients typically suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation, seizures, and intellectual disability; death is less common than with other urea cycle disorders. [pdfs.semanticscholar.org]

  See the Cerebral Palsy and the Intellectual Disability for assessment information and details of therapy. [medicalhomeportal.org]

  For example, some children appear to have more severe intellectual disability while others are more physically affected (e.g. severe spasticity with joint contractures). [rarediseases.info.nih.gov]

• Cerebral Palsy

  Pearls & Alerts for Assessment Spastic diplegia may occur with cerebral palsy or arginase deficiency Children with a clinical presentation of cerebral palsy, particularly the spastic diplegic type, may have arginase deficiency. [medicalhomeportal.org]

  Hyperargininemia is one of the few treatable causes of pediatric spastic paraparesis, and can be confused with cerebral palsy. [pedneur.com]

• Poor Feeding

  Evaluate the newborn (poor feeding, lethargy, hypotonia, tachypnea, seizures, and signs of liver disease). [dnadvent.com]

  Clinical features of the neonatal onset of the disorder include poor feeding, vomiting, lethargy, seizures, tachypnea, coma, and death. [medvik.cz]

  Affected infants typically appear normal at birth, but as ammonia builds up in the body, they develop a lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. [en.wikipedia.org]

  [Summar: 2013] Inheritance Autosomal recessive Primary Care Management Next Steps After a Positive Screen Contact the family and evaluate the infant for poor feeding, vomiting, and lethargy. [medicalhomeportal.org]

  Clinical Presentation of an Acute Hyperammonemic Episode Poor feeding Lethargy Tachypnea Hypothermia Irritability Vomiting Ataxia Seizures Hepatomegaly Coma Hyperammonemic crises in neonates or infants with arginase deficiency are frequently precipitated [newenglandconsortium.org]

• Malnutrition

  In developing countries, diagnosis may be delayed by the assumption that stunting is related to malnutrition alone. CASE PRESENTATION: We describe the diagnosis and treatment of argininemia in a 60-month-old Kaqchikel Maya girl in rural Guatemala. [read.qxmd.com]

  In developing countries, diagnosis may be delayed by the assumption that stunting is related to malnutrition alone.Case Presentation: We describe the diagnosis and treatment of argininemia in a 60-month-old Kaqchikel Maya girl in rural Guatemala. [mendeley.com]

  For these reasons, initial attempts by community health workers to treat this patient for the common malnutrition syndromes were not unreasonable. [bmcpediatr.biomedcentral.com]

  Malnutrition and deficiencies of essential amino acids as well as other essential nutrients are problems associated with treatment for UCDs. [jn.nutrition.org]

  This can happen as a result of anorexia, starvation, malnutrition, or even (in at least one case) as a result of gastric bypass surgery. [easternbiotech.com]

• Increased Energy

  Acute symptoms may occur during prolonged fasting, periods of increased energy demands (fever, stress, lack of sleep), and after meals high in protein. [medicalhomeportal.org]

• Failure to Thrive

  Instead, a slowly progressive appearance of neurological manifestations is seen, starting with irritability, failure to thrive, feeding difficulties, and inability to reach appropriate developmental milestones. [symptoma.com]

  Failure to thrive and dysmorphic features were also seen. Conclusion: Hyperargininemia commonly manifests as regression, failure to thrive, spasticity, seizures with or without microcephaly. [go.gale.com]

  Main features include failure to thrive, signs of hyperammonemia (anorexia, irritability, tachypnea, lethargy, vomiting), and additional neurologic signs (progressive spastic quadriplegia, seizures, mental retardation, hyperactivity). [accessanesthesiology.mhmedical.com]

  Later onset results in milder set of clinical features including vomiting, failure to thrive, irritability, behavioral problems, or psychomotor retardation. Mutations in the ARGININOSUCCINATE LYASE gene cause the disorder. [medvik.cz]

• Liver Dysfunction

  Liver dysfunction was found in four patients, two of whom had mildly elevated blood ammonia levels. Cranial magnetic resonance imaging showed progressive cerebral atrophy in three patients. [scinapse.io]

  Complications include persistent liver dysfunction or central nervous system abnormalities A diagnosis may be established during newborn screening by detecting a higher-than-normal concentration of arginine in blood, which may be the result of Arginase [dovemed.com]

  He has mild liver dysfunction with elevated transaminases and prolonged PT and PTT. Currently the patient has normal physical findings without evidence of spasticity. [ashg.org]

• Muscle Spasticity

  It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles (spasticity). [wikidoc.org]

  It most often appears as stiffness, especially in the legs, caused by abnormal tensing of the muscles ( spasticity ). [research.omicsgroup.org]

  Symptoms typically include poor growth, stiff muscles (spasticity), seizures, loss of skills (developmental regression), and intellectual disability. [myriad.com]

• Incontinence

  Hyperammonemia (though uncommon for it to be >150 µmol/L)) Elevated guanidinoacetate Mild liver dysfunction Subsequent signs and symptoms may include: Poor growth Loss of ambulation Joint contractures Seizures (generalized tonic-clonic) Cognitive decline Incontinence [medicalhomeportal.org]

  Other described symptoms include urinary incontinence and rarely skin rash. CSF usually shows lymphocytic pleocytosis but a normal CSF does not exclude the diagnosis and simply implies that there is no meningeal inflammation [3]. [raredisorders.imedpub.com]

• Urinary Incontinence

  Other described symptoms include urinary incontinence and rarely skin rash. CSF usually shows lymphocytic pleocytosis but a normal CSF does not exclude the diagnosis and simply implies that there is no meningeal inflammation [3]. [raredisorders.imedpub.com]

• Irritability

  Instead, a slowly progressive appearance of neurological manifestations is seen, starting with irritability, failure to thrive, feeding difficulties, and inability to reach appropriate developmental milestones. [symptoma.com]

  Infants may be irritable, vomit and exhibit feeding problems. They may be less alert when given cow's milk. Some infants may refuse to eat. Argininemia will affect the central nervous system. [thinkgenetic.com]

  Other symptoms that may present early in life include episodes of irritability, poor appetite, and vomiting. Severe episodes of hyperammonemia can occur but are infrequent. [rarediseasesnetwork.org]

  This rapid increase in ammonia may lead to episodes of irritability, refusal to eat, and vomiting. In some affected individuals, signs and symptoms of argininemia may be less severe, and may not appear until later in life. [wikidoc.org]

  Work with lung irritants: Those who work with chemicals, dust, smoke, or other lung irritants are at greater risk of hypercapnia. [medicalnewstoday.com]

• Hyperactivity

  More Browse by letters A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 0-9 Other dictionary words English hyped up hyper hyper kid hyperactive hyperactive behaviour hyperactive child hyperactive kids hyperactive thyroid hyperactivity hyperadrenalism [en.bab.la]

  Hyperactivity can be used to describe the increased action of a body function, such as… [tititudorancea.com]

  The major symptoms of AD are all progressive and include psychomotor retardation, spastic tetraplegia where the lower limbs are more affected than the upper, hyperactivity, growth failure and seizures. [themedicalbiochemistrypage.org]

  Main features include failure to thrive, signs of hyperammonemia (anorexia, irritability, tachypnea, lethargy, vomiting), and additional neurologic signs (progressive spastic quadriplegia, seizures, mental retardation, hyperactivity). [accessanesthesiology.mhmedical.com]

• Tremor

  Seizures are common and intellectual disability, tremors, and a condition called spasticity also develop. Spasticity is when there is increased muscle tone and stiffness of leg muscles and can cause muscle spasms. [thinkgenetic.com]

  Argininosuccinic aciduria may become evident in the first few days of life because of high blood ammonia, or later in life presenting with "sparse" or "brittle" hair, developmental delay, and tremors. [icd.codes]

  Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, mental retardation, seizures, tremor, and difficulty with balance and coordination (ataxia). [wikidoc.org]

  Other symptoms may include slower than normal growth, developmental delay and eventual loss of developmental milestones, mental retardation, seizures, tremor, and difficulty with balance and coordination ( ataxia ). [research.omicsgroup.org]

  Elevated CO2, per se, does not seem to cause central nervous system dysfunction with the possible exception of a fine tremor in some patients. [jamanetwork.com]

• Spastic Gait

  Examination revealed a conscious child with intact cranial nerves, bipyramidal signs in lower limbs and spastic gait. Fundi were normal. Her general examination was unremarkable except bilateral parotid enlargement. [annalsofian.org]

  Spastic paraplegia, weakness of bilateral lower limbs, and tip-toeing gait were observed on admission. Protein aversion appeared at the age of 5 years old without any other symptoms. [tp.amegroups.com]

• Lower Extremity Spasticity

  […] limb spasticity, speech delay, intellectual disability • Treated with severe protein restriction, essential amino acids, and ammonia scavengers • Progressive worsening of lower extremity spastic diplegia, ambulates with arm crutches • C.371A>G (single [sec.gov]

Because of the rather rare occurrence of hyperargininemia in clinical practice, the diagnosis might be difficult to attain without adequate clinical suspicion. For this reason, a thorough clinical investigation comprised of a meticulously obtained patient history and a detailed physical examination is of critical importance. The course and progression of symptoms should be assessed with the parents, whereas signs of upper motor neuron damage (hyperreflexia, spasticity) are hallmarks of hyperargininemia on a neurological exam [4]. Furthermore, ataxia, toe walking, and cognitive impairment may be noted [4]. Magnetic resonance imaging (MRI) of the endocranium is a useful procedure in the evaluation of patients suffering from hyperargininemia, showing both cerebral and cerebellar atrophy. Microcephaly could be present in some cases. Electroencephalography (EEG) is also an important component of the diagnostic workup [4], but in order to confirm hyperargininemia, biochemical or genetic testing is necessary. The measured activity of arginase will reveal abnormally low values [4] [5].

Urinary orotic acid concentration Red blood cell arginase enzyme activity (measurement) Treatment[edit] The treatment for infants (individuals) with argininemia is the following, including medications:[3] Protein intake limited Sodium benzoate Sodium [en.wikipedia.org]

In case 2, hyperargininemia was identified through newborn screening and treatment was started when patient was 21 days old. Cholestasis was only identified in the patient's further evaluation and it resolved 2 weeks into treatment. [ncbi.nlm.nih.gov]

Some infants who were diagnosed and treatment from birth have remained symptom-free through a special diet and medication. This will also stop symptoms from getting worse if they have already begun. [thinkgenetic.com]

Once the diagnosis is confirmed, treatment options consist of protein restriction and using alternate techniques to remove nitrogenous wastes as well as supplementing essential amino acids.[7],[8] With the aforementioned treatment, the arginine levels [pediatricneurosciences.com]

European Journal of Human Genetics 6(SUPPL 1): 48, 1998 Diagnosis and treatment of argininemia characteristics of arginase ec 3531 in human erythrocytes and tissues. 1984 Chemically defined diet in the treatment of kwashiorkor. [eurekamag.com]

The prognosis of Arginase Deficiency Disorder is generally good, so long as the necessary dietary restrictions are adhered to and proper medication is taken before symptom onset There are no preventive measures available for this disorder, as it is caused [dovemed.com]

Causes Differentiating Argininemia from Other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Argininemia usually becomes evident by about the age of 3. [wikidoc.org]

Prognosis HIDS has a good prognosis. Life expectancy is not shortened except for in rare cases where severe infections or renal amyloidosis occur. The documents contained in this web site are presented for information purposes only. [orpha.net]

In case 1, diagnosis was established at 2 months of age upon investigation of the etiology of cholestatic injury pattern and hepatosplenomegaly, and treatment was then initiated at when the patient was 3 months old. [ncbi.nlm.nih.gov]

Etiology argininemia is caused by mutation in the gene encoding liver arginase (ARG1) (MIM.608313). Nota bene`: Urea cycle diseases are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. [humpath.com]

Qualificadores Permitidos Inglês: BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology ET etiology [decs.bvsalud.org]

Qualifiers English: BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology ET etiology [decs.bvs.br]

Regarding etiology, NHF is differently classified in the literature, without consensus3,4,6,7. [scielo.br]

Retrieved 20 November 2016.update 2014 ^ a b c d "Arginase Deficiency: Background, Pathophysiology, Epidemiology". eMedicine. 15 April 2016. Retrieved 28 November 2016. ^ a b c Reference, Genetics Home. "ARG1 gene". Genetics Home Reference. [en.wikipedia.org]

Histórica Inglês: 2000 Qualificadores Permitidos Inglês: BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology [decs.bvsalud.org]

Note English: 2000 Allowable Qualifiers English: BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology [decs.bvs.br]

Causes Differentiating Argininemia from Other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Argininemia usually becomes evident by about the age of 3. [wikidoc.org]

[…] novel R21X mutation in the liver-type arginase gene (ARG1) in four Portuguese patients with argininemia. 53 62 5 Cardoso ML...Rocha J 10502833 1999 13 Molecular genetic study of human arginase deficiency. 53 62 5 Grody WW...Leonard JV 1598908 1992 14 Epidemiology [malacards.org]

However, the accumulation of L-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. [agris.fao.org]

Retrieved 20 November 2016.update 2014 ^ a b c d "Arginase Deficiency: Background, Pathophysiology, Epidemiology". eMedicine. 15 April 2016. Retrieved 28 November 2016. ^ a b c Reference, Genetics Home. "ARG1 gene". Genetics Home Reference. [en.wikipedia.org]

However, the accumulation of l-arginine and the resulting abnormalities in the metabolism of guanidine compounds and nitric oxide have been proposed to play a major pathophysiological role. [scinapse.io]

They usually spontaneously adopt a low-protein diet to prevent hyperammonemia. [medicalhomeportal.org]

Perioperative nutrition should aim for high carbohydrate intake and low protein intake to prevent arginine load. To prevent a catabolic state, avoid longer fasting periods and/or cover them with dextrose-containing intravenous solutions. [accessanesthesiology.mhmedical.com]

In a patient with hyperargininemia, oral administration of sodium benzoate or phenylacetic acid together with an essential amino acid mixture was used to prevent hyperammonemia and to decrease plasma and CSF concentrations of arginine. [ncbi.nlm.nih.gov]

Excreting the excess nitrogen prevents it from accumulating in the form of ammonia, which is toxic. [ghr.nlm.nih.gov]

1. Maramattom BV, Raja R, Balagopal A. Late onset arginase deficiency presenting with encephalopathy and midbrain hyperintensity. Ann Indian Acad Neurol. 2016;19(3):392-394.
2. Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005;84(3):243-251.
3. Schlune A, Vom Dahl S, Häussinger D, Ensenauer R, Mayatepek E. Hyperargininemia due to arginase I deficiency: the original patients and their natural history, and a review of the literature. Amino Acids. 2015;47(9):1751-1762.
4. Scaglia F, Lee B. Clinical, Biochemical, and Molecular Spectrum of Hyperargininemia Due to Arginase I Deficiency. Am J Med Genet C Semin Med Genet. 2006;0(2):113-120.
5. Hewson S, Clarke JT, Cederbaum S. Prenatal diagnosis for arginase deficiency: a case study. J Inherit Metab Dis. 2003;26:607–610.
6. Oldham MS, vanMeter JW, Shattuck KF, Cederbaum SD, Gropman AL. Diffusion Tensor Imaging in Arginase Deficiency Reveals Damage to Corticospinal Tracts. Pediatr Neurol. 2010;42(1):49-52.
7. Cederbaum SD, Yu H, Grody WW, Kern RM, Yoo P, Iyer RK. Arginases I and II: do their functions overlap? Mol Genet Metab. 2004;81(Suppl 1):S38–S44.